Purpose:
Leukotriene B4 receptor 2 (BLT2) is a high affinity receptor for 12-hydroxyheptadecatrienoic acid (12-HHT) whose production is inhibited by non-steroidal anti-inflammatory drugs (NSAIDs). We previously reported that BLT2 maintains the barrier function of intestinal epithelial cells. On the other hand, we clinically experience that corneal epithelialization delays in patients treated with NSAIDs. So, we hypothesized that the delayed corneal wound healing in those patients is due to the inhibition of 12-HHT-BLT2 axis in the region. To test this, corneal wound healing was compared between WT and BLT2 KO mice.

Methods:
Expression of BLT2 mRNA in the eye was confirmed in Balb/c WT mice by real-time PCR system. In a wound healing model, WT and BLT2 KO mice on Balb/c background were used for the study. Trephine was used for making 2 mm diameter of wound in cornea of right eye. A circular paper (2 mm diameter) containing n-heptanol was applied to the cornea for 1 min, and epithelial defect was created using a golf blade (MANI Inc.). Each corneal wound was stained by 1% fluorescein and photographed every 8 hours after the surgery until wound was healed. Levofloxacin eye drops (Santen, Osaka, Japan) were used to avoid corneal infection. The area of the epithelial defect was measured using Image J software to quantify the wound healing processes.

Results:
BLT2 mRNA expression was higher in whole eye than in small intestine, but lower than skin. Both cornea and conjunctiva also expressed BLT2. Expression of BLT2 mRNA was higher in cornea than in conjunctiva. The epithelial defects healed within 48 hrs after surgery and healing process of BLT2 KO mice was comparable to that of WT mice.

Conclusions:
We confirmed the significant expression of BLT2 mRNA in Balb/c murine eye. Despite BLT2 is important in barrier function of intestinal epithelial cells, corneal wound healing in mice does not involve 12-HHT/BLT2 axis.